Hyperkalaemia is a common biochemical finding that can allude to pre-analytical or truly pathological causes. Here, we present a case of a 41-year-old female patient who has regularly presented with incidences of isolated hyperkalaemia since 2012, with otherwise normal renal function and no other associated symptoms. Investigations into the patient’s family history revealed similar biochemical findings in her brother and eldest son. Familial causes of hyperkalaemia were investigated and an eventual diagnosis of pseudo-hypoaldosteronism type 2C was established. This is a rare congenital renal tubular disorder, also known as Gordon syndrome, that can cause a characteristic triad of symptoms that include hyperkalaemia, metabolic acidosis and hypertension. The presence and severity of each of these symptoms is dependent upon the disease-causing mutation that occurs in WNK4, WNK1, CUL3 or KLHL3 genes. These mutations alter the regulation of sodium/chloride co-transporter (NCC) expression on the luminal membrane of the principal cells of the distal convoluted tubule, disrupting normal homeostatic regulation of electrolyte reabsorption and excretion. The resolution for treating this condition is the administration of a thiazide diuretic, which directly counteracts the effects of NCC co-transporter overexpression and consequently aims to resolve the symptoms that arise as a result of this aberrant signalling. The case described here uniquely presents an extremely rare pathogenic variant in the conserved acidic motif of WNK1 resulting in a clear electrolyte phenotype with no hypertension.

高钾血症是一种常见的生化发现，可以暗示分析前或真正的病理原因。在这里，我们介绍了一名 41 岁女性患者的病例，该患者自 2012 年以来经常出现单纯性高钾血症，其他方面肾功能正常，没有其他相关症状。对患者家族史的调查显示，她的兄弟和长子也有类似的生化结果。调查了高钾血症的家族性原因，最终诊断为 2C 型假性醛固酮减少症。这是一种罕见的先天性肾小管疾病，也称为戈登综合征，可引起特征性三联征，包括高钾血症、代谢性酸中毒和高血压。这些症状的存在和严重程度取决于 WNK4、WNK1、CUL3 或 KLHL3 基因中发生的致病突变。这些突变改变了远曲小管主要细胞腔膜上钠/氯化物协同转运蛋白 (NCC) 表达的调节，破坏了电解质重吸收和排泄的正常稳态调节。治疗这种情况的解决方案是使用噻嗪类利尿剂，它直接抵消 NCC 共转运蛋白过度表达的影响，从而旨在解决由于这种异常信号传导而出现的症状。这里描述的病例在 WNK1 的保守酸性基序中独特地呈现了一种极其罕见的致病变异，导致电解质表型清晰，没有高血压。